Genome-Wide Characterization and Comparative Analyses of Simple Sequence Repeats among Four Miniature Pig Breeds
ANIMALS
Authors: Wang, Hongyang; Fu, Yang; Gu, Peng; Zhang, Yingying; Tu, Weilong; Chao, Zhe; Wu, Huali; Cao, Jianguo; Zhou, Xiang; Liu, Bang; Michal, Jennifer J.; Fan, Chun; Tan, Yongsong
Abstract
Simple Summary Simple sequence repeats (SSRs) are present at high densities in regulatory elements, suggesting that they may affect gene function and phenotypic traits. Therefore, SSRs can be exploited in marker-assisted selection. In addition, they can be widely used as molecular markers to study genetic diversity, population structure, and evolution. While SSRs have been widely studied in many mammalian species, very little research has focused on genome-wide SSRs of miniature pigs, a small but special group of pigs that express the dwarf phenotype. Based on the SSR-enriched library building and sequencing, about 30,000 novel polymorphic SSRs for four miniature pig breeds were mapped to the Duroc pig reference genome. The four miniature pig breeds had different numbers and types of SSRs and distributions of repeat units. There were 2518 polymorphic SSRs in the intron or exon regions that were common to all four breeds and functional analyses revealed 17 genes that were associated with body size and other genes that were associated with growth and development. In conclusion, the SSRs detected in the miniature pigs in this study may provide useful genetic markers for the selection of farm animals and the polymorphic SSRs provide valuable insights into the determination of mature body size, as well as the immunity, growth and development of animals. Simple sequence repeats (SSRs) are commonly used as molecular markers in research on genetic diversity and discrimination among taxa or breeds because polymorphisms in these regions contribute to gene function and phenotypically important traits. In this study, we investigated genome-wide characteristics, repeat units, and polymorphisms of SSRs using sequencing data from SSR-enriched libraries created from Wuzhishan (WZS), Bama (BM), inbred Luchuan (LC) and Zangxiang (ZX) miniature pig breeds. The numbers and types of SSRs, distributions of repeat units and polymorphic SSRs varied among the four breeds. Compared to the Duroc pig reference genome, 2518 polymorphic SSRs were unique and common to all four breeds and functional annotation revealed that they may affect the coding and regulatory regions of genes. Several examples, such as FGF23, MYF6, IGF1R, and LEPROT, are associated with growth and development in pigs. Three of the polymorphic SSRs were selected to confirm the polymorphism and the corresponding alleles through fluorescence polymerase chain reaction (PCR) and capillary electrophoresis. Together, this study provides useful insights into the discovery, characteristics and distribution of SSRs in four pig breeds. The polymorphic SSRs, especially those common and unique to all four pig breeds, might affect associated genes and play important roles in growth and development.
Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma
CANCERS
Authors: Chuma, Makoto; Uojima, Haruki; Numata, Kazushi; Hidaka, Hisashi; Toyoda, Hidenori; Hiraoka, Atsushi; Tada, Toshifumi; Hirose, Shunji; Atsukawa, Masanori; Itokawa, Norio; Arai, Taeang; Kako, Makoto; Nakazawa, Takahide; Wada, Naohisa; Iwasaki, Shuitirou; Miura, Yuki; Hishiki, Satoshi; Nishigori, Shuhei; Morimoto, Manabu; Hattori, Nobuhiro; Ogushi, Katsuaki; Nozaki, Akito; Fukuda, Hiroyuki; Kagawa, Tatehiro; Michitaka, Kojiro; Kumada, Takashi; Maeda, Shin
Abstract
Predictive biomarkers of the response of hepatocellular carcinoma (HCC) to Lenvatinib therapy have not yet been clarified. The aim of this study was to identify clinically significant biomarkers of response to Lenvatinib therapy, to target strategies against HCC. Levels of circulating angiogenic factors (CAFs) were analyzed in blood samples collected at baseline and after introducing lenvatinib, from 74 Child-Pugh class A HCC patients who received lenvatinib. As CAF biomarkers, serum vascular endothelial growth factor (VEGF), fibroblast growth factor 19 (FGF19), FGF23, and angiopoietin-2 (Ang-2) were measured using enzyme-linked immunosorbent assays. Results: Significantly increased FGF19 (FGF19-i) levels and decreased Ang-2 (Ang-2-d) levels were seen in Lenvatinib responders as compared to non-responders (ratio of FGF19 level at 4 weeks/baseline in responders vs. non-responders: 2.09 vs. 1.32, respectively, p = 0.0004; ratio of Ang-2 level at four weeks/baseline: 0.584 vs. 0.810, respectively, p = 0.0002). Changes in FGF23 and VEGF levels at four weeks versus baseline, however, were not significantly different in responders versus non-responders. In multivariate analysis, the combination of serum FGF19-i and Ang-2-d was the most independent predictive factor for Lenvatinib response (Odds ratio, 9.143; p = 0.0012). Furthermore, this combination biomarker showed the greatest independent association with progression-free survival (Hazard ratio, 0.171; p = 0.0240). Early changes in circulating FGF19 and Ang-2 levels might be useful for predicting clinical response and progression-free survival in HCC patients on Lenvatinib therapy.